The presence of chiral centres in a molecule often leads to different chiral isomers. The larger the number of chiral centres in a molecule the larger the number of different isomers is. In the synthesis of such chiral molecules normally a mixture of chiral isomers is formed. However, very often, it is desirable to separate chiral compounds from each other, for example as they have different properties.
Chroman compounds represent an important class of chiral natural products and bioactive compounds. An important class of chroman compounds are vitamin E and its esters. Often vitamin E is commercialized in the form of its esters because the latter show an enhanced stability.
On the one hand the typical technical synthesis of vitamin E leads to mixtures of isomers. On the other hand higher bioactivity (biopotency) has been shown to occur in general by tocopherols and tocotrienols having the R-configuration at the chiral centre situated next to the ether atom in the ring of the molecule (indicated by * in the formulas used later on in the present document) (i.e. 2R-configuration), as compared to the corresponding isomers having S-configuration. Particularly active are the isomers of tocopherols having the natural configuration at all chiral centres, for example (R,R,R)-tocopherols, as has been disclosed for example by H. Weiser et al. in J. Nutr. 1996, 126(10), 2539-49. This leads to a strong desire for an efficient process for separating the isomers. Hence, the isomer separation not only of vitamin E, but also of their esters, particularly their acetates, as well as of their precursors is of prime interest.
Chromatographic separation of chiral compounds has been found to be an adequate method for the separation of certain chiral isomers as is disclosed by S. K. Jensen in Vitamins and Hormones 2007, Vol. 76, 281-308. Particularly suited for industrial chromatographic separation processes is Simulated Moving Bed (SMB) chromatography as this leads to enhanced separation efficiency and reduced amount of eluent necessary for the separation.
As only a part of the chiral isomers have the desired configuration, any known separation method leads, inherently, only to a small amount of the desired isomer. This amount of a desired isomer gets smaller as the number of chiral centres increases. For explications' sake the following is discussed: if for statistical distribution at each chiral centre is assumed, the amount of the desired isomer is 50% in case of 1 chiral centre, 25% in case of 2 chiral centres, 12.5% in case of 3 chiral centres. As only the desired isomers are the target molecules, the majority of the products synthesized, i.e. the undesired isomers, are typically to be disposed or discarded which is, very costly.
To overcome these inherent problems it has been tried to offer stereospecific synthesis allowing the preferential formation of the desired isomers only. However, these methods are very expensive, complex and/or exotic as compared to the traditional industrial synthesis leading to isomer mixtures.